Intravenous Immunoglobulin (IVIG)

Registered South African indications:

• Primary antibody deficiency syndromes
• Myeloma
• Chronic lymphocytic leukaemia
• Congenital acquired immune deficiency syndrome (AIDS) with recurrent infections
• Idiopathic thrombocytopenic purpura
• Kawasaki disease
• Guillain Barré syndrome
• Allogeneic bone marrow transplantation

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to hyaluronidase or recombinant human hyaluronidase
• Hypersensitivity to corn
• Immunoglobulin A deficiency
• Hyperprolinaemia
• Severe thrombocytopenia or coagulation disorder
• Fructose intolerance

Cautions

• Pregnancy
• Breastfeeding
• Severe renal impairment
• Female patients
• History of migraine
• High doses
• Underlying inflammatory state
• Non-O blood type
• Pre-existing anaemia
• Cardiovascular or respiratory compromise
• Diabetes mellitus
• Overweight patients
• Hypovolemia
• Volume depletion
• Sepsis
• Paraproteinemia
• Risk factors for thrombosis
• Fluid overload

Forms avail. in SA and covered in this monograph: inj

Primary immunodeficiency

• IV: Initial: 0.4-0.8g/kg THEN 0.2-0.8g/kg, as an infusion, every 2-4 weeks

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IgG trough levels of at least 4-6g/L should be obtained

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See additional prescribing points for administration directions

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Secondary immunodeficiency
- Myeloma
- Chronic lymphocytic leukaemia

• IV: 0.2-0.4g/kg, every 3-4 weeks

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IgG trough levels of at least 4-6g/L should be obtained

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See additional prescribing points for administration directions

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Idiopathic thrombocytopenic purpura

• IV: 0.8-1g/kg, as a single dose; Repeat within 3 days if required
  OR
• IV: 0.4g/kg/day, for 2-5 days; Repeat if relapse occurs

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See additional prescribing points for administration directions

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Kawasaki disease (additional agent required)

• IV: 2g/kg, as a single dose
  OR
• IV:1.6-2g/kg, in divided doses for 2-5 days

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See additional prescribing points for administration directions

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Guillain Barré syndrome

• IV: 0.4g/kg/day, for 3-7 days

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See additional prescribing points for administration directions

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Allogenic bone marrow transplantation
- Treatment of infections and prophylaxis of graft versus host disease

• IV: 0.5g/kg, weekly, starting 7 days before transplantation; Treatment duration: Up to 3 months post-transplantation

- Persistent lack of antibody production

• IV: 0.5g/kg, monthly; Treatment duration: Until antibody levels return to normal

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See additional prescribing points for administration directions

Paed. forms avail. in SA and covered in this monograph: inj

Primary immunodeficiency

• IV: Initial: 0.4-0.8g/kg THEN 0.2-0.8g/kg, as an infusion, every 2-4 weeks

---

IgG trough levels of at least 4-6g/L should be obtained

---

See additional prescribing points for administration directions

---

Secondary immunodeficiency
- Myeloma
- Chronic lymphocytic leukaemia

• IV: 0.2-0.4g/kg, every 3-4 weeks

---

IgG trough levels of at least 4-6g/L should be obtained

---

See additional prescribing points for administration directions

---

Children with acquired immune deficiency syndrome (AIDS)

• IV: 0.2-0.4g/kg, every 3-4 weeks

---

See additional prescribing points for administration directions

---

Idiopathic thrombocytopenic purpura

• IV: 0.8-1g/kg, as a single dose; Repeat within 3 days if required
  OR
• IV: 0.4g/kg/day, for 2-5 days; Repeat if relapse occurs

---

See additional prescribing points for administration directions

---

Kawasaki disease (additional agent required)

• IV: 2g/kg, as a single dose
  OR
• IV:1.6-2g/kg, in divided doses for 2-5 days

---

See additional prescribing points for administration directions

---

Guillain Barré syndrome

• IV: 0.4g/kg/day, for 3-7 days

---

See additional prescribing points for administration directions

---

Allogenic bone marrow transplantation
- Treatment of infections and prophylaxis of graft versus host disease

• IV: 0.5g/kg, weekly, starting 7 days before transplantation; Treatment duration: Up to 3 months post-transplantation

- Persistent lack of antibody production

• IV: 0.5g/kg, monthly; Treatment duration: Until antibody levels return to normal

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See additional prescribing points for administration directions

Pregnancy

• Caution
• The safety of this medicinal product for use in human pregnancy has not been established in controlled clinical trials and therefore should only be given with caution to pregnant women. IVIg products have been shown to cross the placenta, increasingly during the third trimester. Clinical experience with immunoglobulins suggests that no harmful effects on the course of pregnancy, or on the foetus, and the neonate, are to be expected

Breastfeeding

• Caution
• Immunoglobulins are excreted into the milk and may contribute to protecting the neonate from pathogens which have a mucosal portal of entry

Renal Impairment

• eGFR ≥30-89ml/min: No dose adjustment recommended
• eGFR ≤29ml/min: Caution; dose adjustment recommended
  Use a weekly or fortnightly protocol; Monitor renal function closely; Discontinue if eGFR <10 ml/min
• For fortnightly dosing (grams): multiply the calculated or previous weekly dose by 2

Hepatic Impairment

• No dose adjustment recommended

Elderly

• No dose adjustment recommended

Porphyria Information

• Not porphyrinogenic (NP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Headache
• Fatigue
• Dizziness
• Insomnia
• Migraine 
• Lethargy
• Fibromyalgia syndrome 
• Malaise 
• Vertigo
• Aseptic meningitis
• Agitation
• Anxiety
• Coma
• Loss of consciousness
• Paraesthesia
• Seizures
• Transient ischemic attacks

Cardiovascular Disorders

• Hypotension
• Tachycardia
• Altered blood pressure
• Decreased heart rate
• Chest pain
• Hypertension 
• Peripheral edema 
• Cardiac arrest
• Heart murmur 
• Chest discomfort 
• Flushing 
• Thrombosis 
• Arterial thrombosis
• Bradycardia
• Cerebrovascular accident
• Circulatory shock
• Cyanosis
• Deep vein thrombosis
• Hypervolaemia
• Myocardial infarction
• Palpitations
• Peripheral vascular insufficiency
• Phlebitis
• Vena cava thrombosis

Respiratory Disorders

• Sore throat
• Cough 
• Nasal congestion 
• Rhinitis 
• Sinusitis 
• Pharyngitis 
• Asthma 
• Upper respiratory tract infection 
• Epistaxis
• Bronchitis 
• Nasopharyngitis
• Rhinorrhea 
• Sinus congestion 
• Nasal mucosa swelling
• Wheezing 
• Tonsil disease 
• Dyspnoea 
• Pharyngolaryngeal pain
• Pneumonia
• Oropharyngeal pain 
• Post nasal drip 
• Throat irritation 
• Acute respiratory distress
• Apnoea
• Hyperventilation
• Hypoxaemia
• Laryngospasm
• Pharyngeal oedema
• Pulmonary oedema
• Pulmonary embolism
• Transfusion-related acute lung injury

Gastrointestinal Disorders

• Abdominal pain
• Diarrhoea
• Nausea and vomiting
• Dyspepsia 
• Gastroenteritis
• Pseudomembranous colitis 
• Gastritis 
• Stomach discomfort 
• Abdominal distress
• Anorexia

Hepatobiliary Disorders

• Increased serum transaminases
• Increased serum alkaline phosphatase
• Decreased serum alkaline phosphatase
• Hyperbilirubinemia 
• Hepatic insufficiency
• Hepatitis
• Jaundice

Genitourinary Disorders

• Nephrolithiasis
• Vulvovaginal candidiasis
• Urinary tract infection
• Cystitis 
• Dysuria 
• Increased serum creatinine
• Increased blood urea nitrogen
• Acute renal failure
• Haematuria
• Haemoglobinuria
• Osmotic nephrosis
• Proximal tubular nephropathy
• Renal tubular necrosis
• Urine discoloration

Endocrine and Metabolic Disorders

• Ketonuria
• Dehydration 
• Increased lactate dehydrogenase

Musculoskeletal Disorders

• Arthralgia
• Limb pain
• Muscle cramps
• Back pain
• Weakness
• Myalgia 
• Muscle spasm
• Myasthenia 
• Neck pain
• Joint effusion 
• Joint swelling
• Tremor

Skin and Subcutaneous Tissue Disorders

• Pruritus
• Ecchymosis
• Purpura
• Petechiae
• Injection site reactions
• Rash
• Cellulitis 
• Urticaria 
• Hyperhidrosis 
• Eczema 
• Xeroderma
• Erythema
• Allergic dermatitis
• Alopecia
• Bullous dermatitis
• Burning sensation
• Epidermolysis
• Erythema multiforme
• Erythematous rash
• Stevens Johnson syndrome

Immune, Blood and Lymphatic System Disorders

• Positive direct Coombs test
• Haemorrhage 
• Thrombocytopenia
• Antibody development
• Fever
• Decreased hematocrit
• Hypersensitivity reaction
• Anaphylactic shock
• Anaphylactoid reaction
• Anaphylaxis
• Angioedema
• Disseminated intravascular coagulation
• Exacerbation of autoimmune pure red cell aplasia
• Haemolysis
• Haemolytic anemia 
• Leukopenia
• Lymphadenopathy
• Pancytopenia

Sensory Disorders

• Otalgia
• Conjunctivitis 
• Eye discharge
• Eye irritation
• Otitis media
• Blurred vision
• Photophobia
• Eye pain
• Retinal thrombosis

• Nephrotoxic agents
• Live vaccines

• Renal function
• Urine output
• Immunoglobulin G levels

Specific cases may require

• Full blood count

Reconstitution procedure

Intravenous Immunoglobulin (IVIG) 1g is supplied with one diluent bag for reconstitution to a 2% solution. IVIG 3g, 6g and 12g are supplied with two diluent bags. To reconstitute to a 3% solution both diluent bags must be used and for a 6% solution only one diluent bag is required

• Remove the closure from the intravenous Immunogloblin bottle and swab the exposed rubber stopper with a suitable antibacterial agent
• Clamp the transfer set and insert the plastic connector into the outlet port of the diluent bag and the needle into the port of the rubber stopper of the IVIG bottle
• Raise the diluent above the IVIG bottle, release the clamp and the vacuum will draw the diluent into the bottle
• Do not use the product if no vacuum is present

IVIG is packed under vacuum. If this vacuum is lost during reconstitution, it may be difficult to reconstitute this product as the diluent flow into the bottle will decrease and eventually stop. Should this occur, insert an airvent needle through the rubber stopper and draw the diluent into the bottle by gravity

• For a 6% solution: Once the transfer of the diluent is complete, remove and discard the transfer set and diluent bag
• For a 3% solution: Once the transfer of the first diluent is complete, re-clamp the transfer set, remove and discard the diluent bag whilst the transfer set remains inserted in the port. Attach the second diluent bag to the transfer set, release the clamp and again the vacuum will draw the diluent into the bottle. Once the transfer of the diluent is complete, remove and discard the transfer set and diluent bag
• Gently swirl the bottle. Do not shake and avoid foaming of the solution. Insert the airvent needle approximately 2mm from the port of the rubber stopper to break the vacuum. Allow the product to stand, swirling occasionally, until completely dissolved
• This may take up to 30 minutes
• The reconstituted solution is slightly opalescent
• Do not use if the solution is turbid or discoloured
• Do not combine with other intravenous preparations
• Infuse immediately after reconstitution
• Infuse the product through an appropriate administration set with an in-line filter, inserted into the port on the rubber stopper of the bottle with the airvent needle in place to vent the infusion

Infusion rate

• The infusion rate recommended is calculated using a 20 drop/ml administration set
• The infusion should be commenced at a rate of 10 to 20 drops per minute (30-60ml/hour), increasing to 20 to 30 drops/minute (60-90ml/hour) after 15 minutes 
• The flow rate may be increased to a maximum flow rate of 40 to 50 drops/minute (120-150ml/hour) if well tolerated by the patient
• Close adherence to the recommended infusion rate is required to prevent adverse reactions. If the rate of infusion is kept low, the risk of side effects is lessened
• Should adverse reactions occur, the administration rate must be decreased or the infusion stopped until the symptoms disappear
• In certain patient groups it is advisable to determine the maximum safe rate of infusion based on the body mass of the patient
• The following administration rate is recommended: 0.01-0.02ml/kg/min for the first 30 minutes, then gradually increased to a maximum of 0.08ml/kg/min for the remainder of the infusion

Intravenous immunogloblin (IVIG) acts as replacement therapy for primary and secondary immunodeficiencies and contains antibodies against multiple antigens (including bacterial, viral, parasitic and mycoplasmal). IVIG interferes with the Fc receptors of reticuloendothelial cells, which is thought to account for its action in autoimmune cytopenias and idiopathic thrombocytopenic purpura. IVIG provides passive immunity by increasing the antibody titre.

Injection (per 50ml) 1g

• Polygam (National Bioproducts)

Injection (per 100ml) 3g

• Polygam (National Bioproducts)

Injection (per 200ml) 6g

• Polygam (National Bioproducts)

Injection (per 400ml) 12g

• Polygam (National Bioproducts)